You are here

Scheduling delegate's final decisions, July 2016

Scheduling medicines and poisons

27 October 2016

Book pagination

2.6 n-Hexane

Part A - Final decisions on matters referred to an expert advisory committee

2. Scheduling proposals referred to the July 2016 meeting of the Advisory Committee on Chemicals Scheduling (ACCS#17)

2.6 n-Hexane

Note

  • Red strikethrough text indicates text that has been deleted.
  • Green italicised text indicates text that has been added.
Referred scheduling proposal

An application was submitted to amend the Schedule 5 entry and create a specific Schedule 7 entry for n-hexane except when packed and labelled for industrial use.

Scheduling history

Historically in Australia, the scheduling of n-hexane has always been covered within another schedule entry and is therefore not separately specified in the SUSMP.

In July 1963, the Poisons Schedule sub-committee decided to include kerosene, mineral turpentine, oil of turpentine, petrol, white spirits, solvent derived from petroleum or coal in Schedule 5.

In November 1991, the National Drugs and Poisons Schedule Committee (NDPSC) agreed that liquid hydrocarbons, when used as a solvent in writing correction fluids packed in containers having a capacity of 20 mL or less, would be exempt from scheduling.

In February 1998, the NDPSC agreed to exempt from scheduling liquid hydrocarbons when used as thinners for writing correction fluids packed in containers having a capacity of 20 mL or less.

In February 2004, the NDPSC considered amending the Schedule 5 liquid hydrocarbon entry to specifically exclude isohexadecane and isododecane, noting that both hydrocarbons are lipophilic and therefore able to dissolve fats present in the skin thereby leading to skin irritation and/or dermatitis. Isododecane is also an eye irritant and both hydrocarbons present as aspiration hazards. The NDPSC therefore decided that the scheduling of isohexadecane and isododecane remain appropriate under the Schedule 5 entry for liquid hydrocarbons and not to amend the Schedule 5 entry to exclude these two hydrocarbons.

Most recently, in June 2007, the NDPSC decided to amend the Schedule 5 liquid hydrocarbon entry to exempt from scheduling liquid hydrocarbon preparations when packed in containers with a capacity of 2 mL or less.

Current scheduling status and other relevant regulations

n-Hexane is not separately specified or listed in the SUSMP. However, it is covered by the following general entries:

Schedule 5

HYDROCARBONS, LIQUID, including kerosene, diesel (distillate), mineral turpentine, white petroleum spirit, toluene, xylene and light mineral and paraffin oils (but excluding their derivatives), except:

  1. toluene and xylene when included in Schedule 6;
  2. benzene and liquid aromatic hydrocarbons when included in Schedule 7;
  3. food grade and pharmaceutical grade white mineral oils;
  4. in solid or semi-solid preparations;
  5. in preparations containing 25 per cent or less of designated solvents;
  6. in preparations packed in pressurised spray packs;
  7. in adhesives packed in containers each containing 50 grams or less of adhesive;
  8. in writing correction fluids and thinners for writing correction fluids packed in containers having a capacity of 20 mL or less; or
  9. in other preparations when packed in containers with a capacity of 2 mL or less.

Appendix E

HYDROCARBONS, liquid

Standard statements: A, G3.

Existing Work Health and Safety Controls for n-hexane
Hazard classification

The chemical is classified as hazardous in the Hazardous Substances Information System (HSIS) (Safe Work Australia), with the following risk phrases for human health:

  • Xi; R38 (irritation);
  • Xn; R48/20 (repeated dose toxicity);
  • Repr. Cat. 3; R62 (reproductive toxicity);
  • Xn; R65 (aspiration hazard); and
  • R67 (Vapours may cause drowsiness and dizziness).
Exposure standards

Australian: The chemical has an exposure standard of 72 mg/m3 (20 ppm) time weighted average (TWA).

International (Galleria Chemica): Exposure limits of 72-1800 mg/m3 (20-500 ppm) TWA and 180–3600 mg/m3 (50-1000 ppm) short-term exposure limit (STEL)/MAK/occupational exposure limit (OEL) in different countries such as Canada, Egypt, France, Netherlands, Norway, Spain, Switzerland and the US.

Scheduling application

General application.

The application's proposed amendments to the SUSMP are as follows:

Schedule 5 - Amend Entry

HYDROCARBONS, LIQUID, including kerosene, diesel (distillate), mineral turpentine, white petroleum spirit, toluene, xylene and light mineral and paraffin oils (but excluding their derivatives), except:

  1. toluene and xylene when included in Schedule 6;
  2. n-hexane, benzene and liquid aromatic hydrocarbons when included in Schedule 7;
  3. food grade and pharmaceutical grade white mineral oils;
  4. in solid or semi-solid preparations;
  5. in preparations containing 25 per cent or less of designated solvents;
  6. in preparations packed in pressurised spray packs;
  7. in adhesives packed in containers each containing 50 grams or less of adhesive;
  8. in writing correction fluids and thinners for writing correction fluids packed in containers having a capacity of 20 mL or less; or
  9. in other preparations when packed in containers with a capacity of 2 mL or less.

Schedule 7 - New Entry

n-HEXANE except when packed and labelled for industrial use.

The applicant's reasons for the request are:

  • n-Hexane may cause lung damage following inhalation exposure;
  • n-Hexane is a skin irritant;
  • n-Hexane is a neurotoxin;
  • n-Hexane causes testicular damage in males;
  • Prohibition for use of n-hexane in cosmetic products internationally. n-Hexane is listed on the following:
    • The Association of South East Asian Nations (ASEAN) Cosmetic Directive Annex II - Part 1: List of substances which must not form part of the composition of cosmetic products;
    • The EU Cosmetics Regulation 1223/2009 Annex II - List of substances prohibited in cosmetic products; and
    • The New Zealand Cosmetic Products Group Standard - Schedule 4: Components cosmetic products must not contain.
  • Alternative chemicals, such as cyclohexane are readily available.
Substance summary

n-Hexane (CAS No. 110-54-3) (Figure 2.6) (synonyms include hexyl hydride and hexane) is a colourless liquid with a gasoline-like odour, used in a wide range of commercial goods in Australia including adhesives (at concentrations up to 60%) and roof cleaning agents, and in the fuel, oil, textiles, furniture, shoemaking and printing industries. Consumer exposure internationally has been identified through its inclusion in cosmetics and in various domestic and commercial products as a solvent and viscosity-decreasing agent (thinner). Also reported are non-industrial uses of n-hexane in non-agricultural pesticides and preservatives. (For the extensive use pattern see the NICNAS IMAP Human Health Tier II assessment report for n-hexane). Exposure may therefore occur by contact with products containing n-hexane and the main routes of exposure are via inhalation and skin contact.

Figure 2.6: Structure of n-hexane

Figure 2.6: Structure of n-hexane

Acute toxicity

Acute toxicity for n-hexane is outlined in Table 2.6. Briefly, acute oral, dermal and inhalation toxicity for n-hexane is low, with LD50's of >15800 mg/kg bw (oral, rat), >2000 mg/kg bw (dermal, rat) and 48000 mg/m3 / 4h (inhalation, rat and mice). As a hydrocarbon with low viscosity, n-hexane is an aspiration hazard with inhalation exposure (5000 ppm/ ~17.6 mg/L, 10 minutes) in humans resulting in vertigo and giddiness, and occupational exposure (1000-25500 ppm = ~3.52-89.76 mg/L, 30-60 min) resulting in drowsiness. Mild skin irritation was observed in humans and eye irritation was seen in rabbits but not observed in humans. Neither mice (local lymph node (LLN) assay), nor humans (25% solution, 25 volunteers), displayed positive skin sensitisation to n-hexane. Repeat-dose toxicity is low based on oral and dermal exposure in animal tests. Neurotoxicity was observed in several animal and human studies and although effects on the central nervous system have been reported, the primary neurotoxic effect of n-hexane is peripheral neuropathy. Peripheral neuropathy was also reported in humans exposed industrially to n-hexane or solvent mixtures containing n-hexane.

The Human Substance Information system (HSIS) classification of n-hexane is hazardous with the risk phrase 'Harmful: danger of serious damage to health by prolonged exposure through inhalation' (Xn; R48/20). In a human inhalation study, approximately 28 % of the inhaled chemical was absorbed from the lungs. The chemical is able to cross the alveolar-capillary membrane and enter the bloodstream easily, with an average half-life of 1.5-2 hours in blood. The final absorption rate is 15-17 % in relation to the total respiratory uptake. In workers exposed to 180 mg/m3 of the chemical, a net lung uptake of 112 mg over eight hours was reported. Approximately 17 % and 20 % of the inhaled chemical was exhaled unchanged in rats and humans, respectively.

n-Hexane is not considered to be genotoxic or carcinogenic (see the NICNAS IMAP Human Health Tier II assessment report for n-hexane for more information) but reproductive toxicity was positive according to a repeat dose study in male rats. n-Hexane is therefore classified as hazardous - Category 3 substance toxic to reproduction - with the risk phrase 'Possible risk of impaired fertility' (Xn; R62) in the HSIS.

Toxicity Species Results SPF (2015) Classification
Acute oral toxicity LD50 (mg/kg bw) Rat >15800 Appendix B
Acute dermal toxicity LD50 (mg/kg bw) Rat >2000 Appendix B
Acute inhalational toxicity LC50 (mg/m3/4h) Rat, Mice 48000 ppm (~ 169.2 mg/L) Schedule 7
Inhalation exposure (5000 ppm/ ~17.6 mg/L, 10 min) Humans Vertigo, giddiness N/A
Occupational exposure (1000-25500 ppm or approximately 3.52-89.76 mg/L) Humans Drowsiness N/A
Skin irritation Human Mild irritant Schedule 5
Eye irritation Rabbit Not irritating* Appendix B
Skin sensitisation (LLNA) Mice Not sensitising* Appendix B or Schedule 5
Skin sensitisation (Maximisation Test) Human Not sensitising* Appendix B or Schedule 5
Genotoxicity Rat Not genotoxic* N/A
Carcinogenicity Rats, Mice Not carcinogenic* N/A
Reproduction and developmental toxicity Rats Positive N/A

* See the NICNAS IMAP Human Health Tier II assessment report for n-hexane for more information.

Pre-meeting public submissions

Four (4) public submissions were received and all were opposed to the proposed Schedule 7 entry because of the substances wide use. Two (2) advocated the use of exemptions to manage the risks of the varied and diversified end-use products. One (1) proposal states that, because there are no proposed concentration limits, any product containing even trace amounts of n-hexane, including vegetable oil, would need to be labelled as a Dangerous Poison.

Summary of ACCS advice to the delegate

The committee advised that the current scheduling for n-hexane remains appropriate. Members agreed that the relevant matters under Section 52E (1) of the Therapeutic Goods Act 1989 included: (a) the risks and benefits of the use of a substance; (b) the purposes for which a substance is to be used and the extent of use of a substance; (c) the toxicity of a substance; and (d) the dosage, formulation, labelling, packaging and presentation of a substance; and (e) the potential for abuse of a substance.

The reasons for the advice included:

  • Limited data surrounding n-hexane-induced neurotoxicity in humans. The risks are not consistent with the creation of a new Schedule 7 entry;
  • Use patterns indicate limited exposure to n-hexane in the domestic market. Multiple industrial uses of n-hexane including in petrol and some foods (in small quantities);
  • Low acute toxicity via the oral, dermal and inhalation routes; and
  • Mild skin irritant.
Delegate's considerations

The delegate considered the following in regards to this proposal:

  • Scheduling proposal;
  • ACCS advice;
  • Public submissions received;
  • Section 52E of the Therapeutic Goods Act 1989;
  • Scheduling Policy Framework (SPF 2015); and
  • Other relevant information.
Delegate's interim decision

The delegate notes and accepts the ACCS advice that the current scheduling for n-hexane remains appropriate. Owing to the limited data surrounding n-hexane-induced neurotoxicity in humans, the risks are not consistent with the creation of a new Schedule 7 entry. n-Hexane is currently covered by the general Schedule 5 entry for hydrocarbons owing to n-hexane's low acute toxicity via the oral, dermal and inhalation routes and status as a mild skin irritant. Furthermore, the use patterns of n-hexane (including industrial uses in petrol and some foods) indicate limited exposure in the domestic market.

An implementation date is not relevant given the substance is already covered by the generic hydrocarbons Schedule 5 entry.

The delegate considered the relevant matters under section 52E (1) of the Therapeutic Goods Act 1989: (a) the risks and benefits of the use of a substance; (b) the purposes for which a substance is to be used and the extent of use of a substance; (c) the toxicity of a substance; and (d) the dosage, formulation, labelling, packaging and presentation of a substance; and (e) the potential for abuse of a substance.

Public submissions on the interim decision

Two (2) public submissions were received regarding the interim decision that the current scheduling for n-hexane remains appropriate, one in support of the decision and one which opposed the decision on the basis of the neurotoxic potential to humans.

Delegate's final decision

The delegate has confirmed the interim decision as no evidence has been received to alter the interim decision. The delegate has confirmed that the final decision and reasons are in keeping with those for the interim decision.

The implementation date is 1 February 2017.

AttachmentSize
Image icon (jpg)2KB

Book pagination